832712-40-0Relevant articles and documents
Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 3′-substituted deschloroepibatidine analogues. Novel nicotinic antagonists
Carroll, F. Ivy,Ma, Wei,Yokota, Yasuno,Lee, Jeffrey R.,Brieaddy, Lawrence E.,Navarro, Hernán A.,Damaj,Martin, Billy R.
, p. 1221 - 1228 (2005)
A series of 3′-substituted deschloroepibatidine analogues (3a-g and 4) showed high affinity for α4β2 binding and relatively weak affinity for α7 nAChRs. The 3′-ethynyl (3g) and 3′-fluoro (3a) analogues with Ki values of 0.02 and 0.037 nM, respectively, were the most potent. Even though the α4β2 binding affinity of several of the analogues were equal to that of epibatidine, all of the compounds were weak agonists in the antinociceptive, hypothermia, and spontaneous activity test in mice. In contrast, all of the compounds were functional antagonists of nicotine-induced antinociception. In general, compounds 3a-g and 4 were more potent in the tail-flick assay than the hot-plate test. For example, the 3′-fluoro analogue 3a and the N-methyl-3′-iodo analogue 4 showed AD50 values of 0.07 and 0.04 μg/kg, respectively, in the tail flick test and only 35 and 0% inhibition at 20 and 10 μg/kg in the hot-plate assay, respectively. These results suggest that these compounds will be highly useful for identifying which specific receptor subtypes are involved in each of nicotine's pharmacological effects. The high affinity of the N-methyl-3′-iodo analogue 4 combined with its weak agonist and potent antagonist activity suggests that carbon-11 and iodine-123 analogues may be useful as PET and SPECT ligands, respectively, for studying nAChRs in vivo.
LIGANDS FOR NICOTINIC ACETYLCHOLINE RECEPTORS, AND METHODS OF MAKING AND USING THEM
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Page 94, (2010/02/10)
One aspect of the present invention relates to heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. A second aspect of the invention relates to the use of a compound of the invention for modulation of a mammalian nicotinic acetylcholine receptor. The present invention also relates to the use of a compound of the invention for treating a mammal suffering from Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism or trichtillomania.
